The hypothesis that viral infection of a genetically susceptible host can result in juvenile diabetes is supported by the abrupt onset, the seasonal incidence, the presence of inflammatory cells in the islets of Langerhans and the destruction of beta cells. Recently, a strain of Coxackievirus B4 which caused diabetes in mice was isolated from the pancreas of a child with diabetic ketoacidosis. Also, a serologic relationship between Coxsackie B4 and B3 infection and juvenile-onset diabetes have been reported. Several strains of the Coxsackie B viruses have a tropism for murine pancreatic tissue, some destroying acinar tissue primarily, and others causing insulitis. It is clear that diabetogenic strains of Coxsackie virus exist in nature. The specific aims of this proposal are to acquire field strains of the Coxackieviruses capable of causing diabetes in susceptible mice by testing 60 clinical isolates of common Coxsackie B virus serotypes. The second specific aim is to describe the pancreatic pathology produced by diabetogenic strains. The third specific aim is to plague purify and characterize human picornavirus variants that differ in their ability to cause diabetes. The proposed studies of field strains of the human Coxsackie viruses using a sensitive animal model wil provide an estimate of the prevalence of such strains and should help to determine the importance of Coxsackievirus-induced human diabetes mellitus. This information will help in the design of future studies in newly diagnosed juvenile diabetics aimed at establishing a viral etiology. Finally, the availability of diabetogenic variants of human Coxsackievirus strains would open many new lines of investigation aimed at determining the properties responsible for diabetogenicity.